{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T14:03:40Z","timestamp":1793714620124,"version":"4.6.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Fourth People\u2019s Hospital, Tongji University","award":["SY-XKZT-2021-1008"],"award-info":[{"award-number":["SY-XKZT-2021-1008"]}]},{"name":"Shanghai Fourth People\u2019s Hospital, Tongji University","award":["SYKYQD03001"],"award-info":[{"award-number":["SYKYQD03001"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis-associated acute kidney injury (SA-AKI) is a common and severe complication of sepsis, yet early predictors remain limited. Lactate, beyond being a marker of tissue hypoperfusion, may act as a signaling molecule through protein lactylation. This study aimed to investigate the association between lactate levels and SA-AKI risk using the MIMIC-IV database and to explore the potential mechanistic role of lactylation in septic mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adult sepsis patients were identified from the MIMIC-IV (v3.1) database. Patients were stratified by lactate tertiles within 24\u202fh of ICU admission, and lactate clearance (LC) was assessed as a dynamic indicator. The primary outcome was SA-AKI, and secondary outcomes included CRRT use and 28-day mortality. Kaplan\u2013Meier analysis, Cox regression, and restricted cubic spline (RCS) models were performed. In parallel, a murine cecal ligation and puncture (CLP) model was used to evaluate tissue-specific protein lactylation by Western blot, along with serum lactate and hematological parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 11,431 patients were included. Higher lactate levels were associated with increased disease severity, higher incidence and severity of SA-AKI, greater use of CRRT, and elevated 28-day ICU and in-hospital mortality. In Cox regression, lactate as both a continuous and categorical variable was independently associated with SA-AKI risk. RCS analysis revealed nonlinear dose\u2013response relationships, with sharply increased risk of SA-AKI above 5.7\u202fmmol\/L. In sensitivity analyses (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f6,593), higher LC was associated with lower risks of SA-AKI, CRRT use, and mortality. Cox regression confirmed LC as an independent protective factor, while RCS suggested a downward but non-significant trend. In the CLP mouse model, protein lactylation was markedly elevated in the kidney but not in the heart, liver, or spleen, accompanied by higher serum lactate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Elevated lactate levels are independently associated with increased risk of SA-AKI in sepsis patients, whereas higher lactate clearance is linked to improved renal outcomes. Moreover, kidney-specific upregulation of protein lactylation in septic mice suggests a possible molecular link between lactate metabolism and renal vulnerability. These findings highlight lactate and lactylation as both prognostic markers and potential mechanistic contributors in SA-AKI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1708145","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T06:22:35Z","timestamp":1763101355000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Lactate and lactylation in sepsis-associated acute kidney injury: clinical evidence from the MIMIC-IV database and mechanistic insights"],"prefix":"10.3389","volume":"12","author":[{"given":"Sujing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqing","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1164\/rccm.201504-0781OC","article-title":"Assessment of global incidence and mortality of hospital-treated sepsis. 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